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PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition

PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A rat renal tubular epithelial cell line, NRK52E, was transfected with len...

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Autores principales: Hou, Ling, Du, Yue, Zhao, Chengguang, Wu, Yubin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133107/
https://www.ncbi.nlm.nih.gov/pubmed/30117015
http://dx.doi.org/10.1007/s11255-018-1956-0
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author Hou, Ling
Du, Yue
Zhao, Chengguang
Wu, Yubin
author_facet Hou, Ling
Du, Yue
Zhao, Chengguang
Wu, Yubin
author_sort Hou, Ling
collection PubMed
description PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A rat renal tubular epithelial cell line, NRK52E, was transfected with lentivirus carrying PAX2, and E-cadherin and α-SMA expressions were measured. The influence of PAX2 on ADAM10 promoter activity was evaluated using chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assay. We also treated NRK52E with ADAM10-specific over-expression vector and inhibitors and measured E-cadherin and α-SMA expression. In vivo, Wistar rats (n = 36) were subjected to unilateral ureteral obstruction (UUO) (n = 18) or sham surgery (n = 18), with tissues from post-operative day 3, 7, and 14 days examined, and PAX2/ADAM10 activity measured. ADAM10 expression was also assessed in kidneys from patients with chronic kidney disease (CKD). RESULTS: In NRK52E overexpressing PAX2, ADAM10 and α-SMA levels were increased, while E-cadherin levels were decreased. CHIP and dual-luciferase reporter assay showed that PAX2 directly bound to a specific site within the ADAM10 promoter, and over-expression of PAX2 significantly activated ADAM10 transcription. NRK52E with ADAM10 over-expression also significantly decreased E-cadherin and increased α-SMA levels. In the fibrotic kidneys of rats with UUO, E-cadherin levels were increased and α-SMA levels were decreased, and expression of PAX2 and ADAM10 increased. ADAM10 expression also elevated in the renal tissues of CKD patients. CONCLUSIONS: PAX2 directly increased expression of ADAM10, the presence of which contributed to EMT in renal tubular epithelia and hence plays an important role in renal fibrosis.
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spelling pubmed-61331072018-09-18 PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition Hou, Ling Du, Yue Zhao, Chengguang Wu, Yubin Int Urol Nephrol Nephrology - Original Paper PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A rat renal tubular epithelial cell line, NRK52E, was transfected with lentivirus carrying PAX2, and E-cadherin and α-SMA expressions were measured. The influence of PAX2 on ADAM10 promoter activity was evaluated using chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assay. We also treated NRK52E with ADAM10-specific over-expression vector and inhibitors and measured E-cadherin and α-SMA expression. In vivo, Wistar rats (n = 36) were subjected to unilateral ureteral obstruction (UUO) (n = 18) or sham surgery (n = 18), with tissues from post-operative day 3, 7, and 14 days examined, and PAX2/ADAM10 activity measured. ADAM10 expression was also assessed in kidneys from patients with chronic kidney disease (CKD). RESULTS: In NRK52E overexpressing PAX2, ADAM10 and α-SMA levels were increased, while E-cadherin levels were decreased. CHIP and dual-luciferase reporter assay showed that PAX2 directly bound to a specific site within the ADAM10 promoter, and over-expression of PAX2 significantly activated ADAM10 transcription. NRK52E with ADAM10 over-expression also significantly decreased E-cadherin and increased α-SMA levels. In the fibrotic kidneys of rats with UUO, E-cadherin levels were increased and α-SMA levels were decreased, and expression of PAX2 and ADAM10 increased. ADAM10 expression also elevated in the renal tissues of CKD patients. CONCLUSIONS: PAX2 directly increased expression of ADAM10, the presence of which contributed to EMT in renal tubular epithelia and hence plays an important role in renal fibrosis. Springer Netherlands 2018-08-16 2018 /pmc/articles/PMC6133107/ /pubmed/30117015 http://dx.doi.org/10.1007/s11255-018-1956-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Nephrology - Original Paper
Hou, Ling
Du, Yue
Zhao, Chengguang
Wu, Yubin
PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title_full PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title_fullStr PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title_full_unstemmed PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title_short PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
title_sort pax2 may induce adam10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition
topic Nephrology - Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133107/
https://www.ncbi.nlm.nih.gov/pubmed/30117015
http://dx.doi.org/10.1007/s11255-018-1956-0
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